mTOR signaling: PLD takes center stage.
The mammalian target of rapamycin (mTOR) assembles a signaling network that transduces nutrient signals and various other stimuli to regulate a wide range of cellular functions. Of the two distinct mTOR complexes, mTORC1 is under the control of the TSC-Rheb pathway, which serves as an integrator of multiple upstream signals. A lipid signaling cascade involving phospholipase D (PLD) and phosphatidic acid (PA) has also been known to mediate mitogenic signals upstream of mTORC1. A new study now reveals a direct connection between these two regulatory pathways and demonstrates that PLD1 is an effector of Rheb in the activation of mTORC1. A novel role of PLD as a nutrient sensor has also been suggested. In this extra-view, we discuss the emerging importance of PA and PLD in the mTORC1 signaling network and the biological processes it governs. We also consider the implications from several recent findings and propose mechanistic models of PLD-mTOR signaling to be tested in the near future.
Sun
Yuting
Y
Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
Chen
Jie
J
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D010712:Phosphatidic Acids / Q000378:metabolism; D010739:Phospholipase D / Q000378:metabolism*; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
D000596:Amino Acids; D007527:Isoenzymes; D010712:Phosphatidic Acids; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D010739:Phospholipase D; D020559:Monomeric GTP-Binding Proteins